Synthetic Approaches to Understand Cis-regulation
The Kosuri Lab develops technologies to make it easier to read, write and edit DNA. We use these technologies to study how genomic sequences control the regulation of gene expression. In particular, we develop methods to build large libraries of synthetic DNA sequences using low-cost DNA microarrays. This allows us to build thousands to millions of designed variants of regulatory control regions. Each of these synthetic constructs is essentially a hypothesis for how changing the sequence might affect regulatory function. Second, we develop new next-generation sequencing-based methods that allow us to quantitate the functionality of these synthetic DNA libraries in a pooled format. For example, we have developed methods to measure large pools of synthetic reporter constructs analyzing processes such as transcription, translation, and splicing. Finally, using new genomic engineering technologies, we can do these large-scale synthesis/sequencing experiments in a wide-variety of cell types such as bacteria, yeast, and human cell lines. We combine these technologies to test models for how combinations of regulatory elements and mechanisms combine to control the regulation of gene expression.